PROJECT SUMMARY (30 lines only) The World Health Organization recommends that all HIV-infected pregnant women receive lifelong antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT-ART, formerly Option B+). Pre-exposure prophylaxis (PrEP) is also recommended by the WHO for all HIV-uninfected pregnant women with a high risk of HIV acquisition. HIV treatment and prevention among special populations, including pregnant women, are also high priorities in the NIH?s HIV research Trans-Plan. As PMTCT-ART expands and PrEP rolls out globally, the likelihood of pregnant women on antiretrovirals (ARVs) will substantially increase. Little is known, however, about the degree of transfer of maternal ARVs to infants during pregnancy. Such information could be useful for identifying the optimal maternal ART regimens to use during pregnancy to maximize infant protection against HIV while minimizing potential toxicities. As a monitoring matrix, neonatal hair can successfully quantify prenatal exposure to maternal medications in utero over time. To date, hair analysis has not been harnessed to evaluate rates of maternal to infant ARV transfer. The proposed study aims to quantify maternal-to-infant transfer during pregnancy for a variety of ARVs by employing a novel pharmacokinetic evaluation using maternal and neonatal hair in an unprecedented cohort. We will use validated assays developed by our group to measure ARV levels in hair samples collected at birth from mother-infant pairs enrolled in the Surveillance Monitoring for ART Toxicities Study in HIV-uninfected Children Born to HIV-infected Women (SMARTT Study), a Pediatric HIV/AIDS Cohort Study (PHACS)-funded prospective study designed to evaluate the effects of ARV exposure on infants born to HIV-infected mothers in the U.S. Leveraging data from this important cohort, we will quantify the extent of mother-to-infant transfer of different ARVs in utero through a paired analysis of mother and neonate hair samples collected at infant delivery (Aim 1) using validated liquid chromatography/tandem mass spectrometry (LC-MS/MS)-based methods. We will further assess the extent of correlation between maternal and infant hair concentrations for each ARV (specifically, for tenofovir [TFV], emtricitabine [FTC], lopinavir [LPV], ritonavir [RTV], atazanavir [ATV], darunavir [DRV], raltegravir [RAL], dolutegravir [DTG], efavirenz [EFV] and nevirapine [NVP]). In Aim 2, we will evaluate whether in utero mother- to-infant transfer of ARVs differs by type or class of ARV and determine whether others characteristics influence the degree of transfer including duration of ARV use, concomitant medications, maternal CD4 count and HIV RNA level during pregnancy, and use of substances, psychotropic medications, or alcohol during pregnancy. We are uniquely positioned in this application to conduct these aims by leveraging an existing repository of collected hair samples from the SMARTT Study among mother-infant pairs. Our results will improve understanding of maternal-to-infant transfer for common ARVs used during pregnancy with ultimate implications for worldwide efforts to prevent perinatal HIV transmission with maximum efficacy and minimal toxicity.